PROJECT SUMMARY: The overriding theme of this CMCR is ultra high-throughput biodosimetry. It is well established that this is a central and necessary component of any effective response to a large scale radiological-event. In the 4+ years that this CMCR program has been in existence, we have Achieved a biodosimetry sample throughput of 6,000 samples per day, and are on target for 30,000 samples per day in 2010. Throughputs with currently available standard biodosimetry approaches are typically <100/day. Demonstrated, for the first time, the ability of a single gene set to predict radiation dose, throughout a significant window of time post exposure, without the need for individual pre-exposure controls. Demonstrated the potential for a urine-based metabolomics biodosimetry system, with signals increasing in a dose-response manner, and with a signal lifetime of at least several days. Our initial application focused exclusively on external whole-body photon irradiation. One of the main themes of this renewal application is to assess the significance of the variety of other radiation scenarios that are likely to occur, in particular the effects of partial-body exposure, internal emitters, low dose rate, and neutron exposure. In that we have developed high-throughput systems for using various biomarkers for biodosimetry, we are now in a unique position to probe the application of these biomarkers for predicting inter-individual sensitivity to acute radiation syndromes. We have two interlaced motivations here;The first is to investigate correlations between our high-throughput biomarkers and individual acute radiation sensitivity, and the second is to probe the associated mechanisms. Both of these approaches build on - and would not be possible without - the high-throughput biodosimetry work that we have accomplished to date.